AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Translational Res 2010;2(4):447-457

Review Article
Epoxyeicosatrienoic acids and soluble epoxide hydrolase: potential
therapeutic targets for inflammation and its induced carcinogenesis

Stephanie Norwood, Jie Liao, Guang-Yu Yang

Department of Pathology, Northwestern University, Feinberg School of Medicine, 303 East Chicago Avenue,
Chicago, IL 60611, USA.

Received June 15, 2010; accepted July 20, 2010; available online July 22, 2010

Abstract: Chronic inflammation is an important factor contributing to human carcinoma, and non-steroidal
anti-inflammatory drugs (NSAIDs) have been shown to have a preventive effect in the development of various
types of carcinoma.  However, NSAIDs also have adverse side effects including increased cardiovascular events,
making them less than ideal for routine chemoprevention.  Soluble epoxide hydrolase (sEH) is an enzyme that
converts endogenous anti-inflammatory compounds, the epoxyeicosatrienoic acids (EETs), to the less
anti-inflammatory dihydroxyeicosatrienoic acids (DHETs).  Inhibition of sEH, by a highly selective and potent sEH
inhibitor (sEHI), increases EETs leading to decreased inflammation.  In our studies, administration of a sEHI in
mouse colitis models led to decreased ulcer incidence and number of ulcers compared to controls, with no
adverse side effects seen.  In human tissue, sEH showed an increase in expression, as seen
immunohistochemically, in ulcerative colitis (UC), UC-induced dysplasia, and UC-induced carcinoma.  Thus,
inhibition of sEH may be a novel biomarker and potential therapeutic target in inflammation and
inflammation-induced carcinoma. (AJTR1006001).

Key words: Epoxyeicosatrienoic acids (EETs), soluble epoxide hydrolase (sEH), dihydroxyeicosatrienoic acids
(DHETs), inflammation, non-steroidal anti-inflammatory drugs (NSAIDs), therapy, carcinogenesis, cancer

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Address all correspondence to:
Guang-Yu Yang, M.D., Ph.D.
Department of Pathology
Northwestern University
Feinberg School of Medicine
303 E. Chicago Avenue
Chicago, Il 60611
Tel: 312-503-0645
Fax: 312-503-0647
E-mail:
g-yang@northwestern.edu